title: beta-adrenoreceptor blocking and antihypertensive activity of PP-24, a newly synthesized aryloxypropanolamine derivative.
abstract: PP-24 is a newly synthesized putative beta-adrenoceptor antagonist. The objective of the study was to the evaluate beta-adrenoceptor blocking activity of PP-24 on isolated rat preparations: right atria, uterus and colon. Effects on the rat ECG and renal hypertension (induced by left renal artery ligation) were also investigated. Treatment with PP-24 (3 and 10 mg kg(-1)) for 7 days in rats with renal hypertension significantly reduced the mean atrial blood pressure. Single i.v. injections of isoprenaline (0.3, 1 and 3 microg kg(-1)) alone in normal anaesthetized rat caused hypotension and tachycardia, while PP-24 alone produced dose-dependent falls in mean aterial pressure and bradycardia. Pretreatment of anaesthetized rats with test compounds significantly blocked the hypotension response but not the tachycardia induced by isoprenaline (0.3, 1 and 3 microg kg(-1)). The pA(2) of PP-24 to beta(1)-, beta(2)- and beta(3)-adrenoceptors was 7.72 +/- 0.082, 7.40 +/- 0.082 and 6.39 +/- 0.16, respectively. The beta(1)/beta(2) selectivity ratio was 2.08, compared with 1.27 for propranolol and 39.17 for atenolol. It is concluded that PP-24 possesses beta-adrenoceptor blockade activity but with non-specific affinity for beta(1)- and beta(2)-adrenoceptor subtypes. The rank order of potency of the antagonists for beta(1)-adrenoceptors was atenolol > PP-24 > propranolol. The antihypertensive activity of PP-24 in rats with renal hypertension appears to be due to blockade of beta-adrenoceptors.
authors.affiliation: Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth University, Erandwane, Pune - 411038, India.
authors.forename: Aniket P
authors.initials: AP
authors.lastname: Nikam
authors.forename: Subhash L
authors.initials: SL
authors.lastname: Bodhankar
authors.forename: Poonam
authors.initials: P
authors.lastname: Piplani
authors.forename: Jyotika
authors.initials: J
authors.lastname: Bansal
authors.forename: Prasad A
authors.initials: PA
authors.lastname: Thakurdesai
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001596:Benzylamines / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006977:Hypertension, Renal / Q000188:drug therapy*; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
chemical_list: C533906:1-(isopropylamino)-3-(5-((isopropylamino)methyl)-2-methoxyphenoxy)propan-2-ol; D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D001596:Benzylamines; D011412:Propanolamines; D001262:Atenolol; D011433:Propranolol; D007545:Isoproterenol